Abstract:

A composition of macrocyclic oligomer with at least one polymerizable
group, (meth)acrylate, for example.

Claims:

1. A dental composition comprising a macrocyclic oligomer with at least
one (meth)acrylate polymerizable group.

2. A method of preparing a dental composition comprising a polymerizable
macrocyclic oligomer, comprising the step of preparing an activated
precursor of an oligomer at pseudo high-dilution conditions.

3. A method claimed in 2, wherein said activated precursor is liquid,
crystalline solid or a combination of both.

4. A method as in claim 2, wherein said precursor itself is polymerizable.

5. A method as in claim 2, comprising the step of reacting said precursor
with a coupling agent selected from the group consisting of primary
diols, secondary amines, diacids and combinations thereof.

6. A method as in claim 5, wherein said coupling agent is aliphatic,
aromatic or both.

7. A method of preparing a dental composition comprising a polymerizable
macrocyclic oligomer, comprising the step of preparing an activated
precursor of an oligomer by reacting said precursor with an activated
coupling agent, wherein said precursor is condensable and polymerizable.

[0002]This invention relates to a composition that can primarily be used
in dental composite to afford low curing shrinkage and low curing stress.
More specifically, it includes a method to prepare new resin that
features by its macrocyclic geometry. In addition it also includes a
method to prepare another resin diluent that features by its bulky,
cyclic, and mono polymerizable group. Of course, a resin composition
containing the macrocyclic oligomer and the bulky diluent and a
resin/filler composition thereafter, which feature by low shrinkage AND
low stress, are included as well. The unique structural geometry of
polymerizable macrocyclic oligomer determines its low shrink nature; and
its unique structural combination with a bulky diluent enables low shrink
accompany with low stress. The application of such a resin composition
will not limit in dental composites or other application in restorative
dentistry such as resin cement, bonding agent, liner, et al. It can be
extended to any other field, in which low shrink and low stress is as
critical as in restorative dentistry.

BACKGROUND OF THE INVENTION

[0003]Polymerization shrinkage of curable material is referred to the
dimensional contraction during polymerization prior to the cured
objective is developed. The covalent bond formation during polymerization
bring monomer molecules closer than what they were in the normal van der
Walls distance. This is the origin of polymerization shrinkage and it is
also the origin of polymerization stress. Of course, the stress
accumulation depends on how the materials are cured, that is, the
polymerization kinetics.

[0004]The chemical structure of a curable resin determines almost every
property aspects for any cured objectives in certain extend. Then it
comes with the process or technology through which the curing proceeds.
Formulation is a process primarily regarding as a balance between
individual ingredient and acceptable property by adjusting the
composition. A process that integrates all components together should be
included in the formulation stage as well. Other emerging parameters
involved during the polymerization process such as curing light intensity
and curing time and curing mode, definitely would affect any property
associated the polymerization like shrinkage, stress and mechanical
property. In this invention, only composition formulation part is
covered. More particularly it regards new resin development and composite
formulation thereafter.

[0005]It is well known that with increasing molecular weight, the mobility
of polymeric chain would be limited, the diffusion is becoming the rate
control factor. In addition, such a limited mobility in a cross-linking
system appear to come earlier in comparison with linear system, which
means extra reaction would lead to an increasing polymerization stress.
There are different ways to control the stress generation and
development:

[0006]1. Limit polymerization rate; [0007]Introducing a special rate
controller like stable radicals; [0008]Creating different polymerization
zones from which the stress developed in a polymerized zone could be
transferred to its adjacent unpolymerized zone and got relief like
segmental polymerization technique; [0009]Employing different
polymerization groups; [0010]Using macromonomer to limit its reactivity
at the early stage;

[0011]2. Limit polymerization conversion;

[0012]3. Limit cross-link density;

[0013]To reduce polymerization shrinkage and stress in the dental
restorative composite, all of above approaches are taking into account as
regards of chemistry approach. Besides, there is significant advance in
the aspects of filler since it is composed of 60-90% in the entire
composite. Increasing filler loading would lead to increasing in
mechanical strength and reduction in polymerization shrinkage.
Furthermore, the nature of filler, such as chemical composition, particle
size and size distribution, surface character, silanization degree et al,
have also demonstrated a tremendous impact on the balance between
mechanical strength and shrinkage.

[0014]There is increasing demand for low shrinkage dental composite, since
it was suggested that the lower polymerization shrinkage, the lower
curing stress, then the higher clinically success in tooth restoration.
However, such a correlation is not always true, this recommendation
should be cautions. It is known that such recommendations for dental
materials and clinical application techniques are frequently based on
laboratory tests. However, if the lab test were based different methods,
the recommendation would not make any sense. More specifically at the
time being there is no standard method to evaluate the shrinkage and
stress for dental materials, it should not be surprised to question any
recommendation for particular dental material or product. Low shrinkage
does not necessary grantee you low stress and less failure if the
clinical operation is not proper, that it still quite technique sensitive
procedure, not every clinician do it right. Just as an example, a new low
shrinkage resin builds the foundation to a low shrinkage composite, but
that does not assure that a low shrinkage product because the formulation
and other associated technology can make it happen. Otherwise, the low
shrinkage resin only means a good paper or paten, That is all. Same
logical could be applied to tooth restoration with low shrinkage or even
zero shrinkage composite, which is the base for a successful restoration
but does not guaranteed it because it need highly trained clinician make
it happen.

[0015]Polymerization shrinkage measurement is critical during low shrink
material development, because it is important for establishing a reliable
correlation between shrinkage and stress. It also helps for a fair
judgement on low shrinkage composite to either clinician as dental
material researchers. Unfortunately, there is no standard method by which
polymerization shrinkage for resin or composite can be examined. Mercury
dilatometer and gas pycnometer is employed in this laboratory to evaluate
the polymerization shrinkage of resin and composite.

[0016]There are two different approaches to limit polymerization shrinkage
and stress: chemical approach and technology approach. For light curable
dental composite for instance, the chemical approach include new curing
groups, new structural frames, new photoinitiator, new reaction kinetics,
new coupling agent for new interface interaction between resin and
fillers, and new filler et al; and technology approach includes: new
curing light source, new curing energy, new curing mode, new technique to
create a cavity, new technique to fill the cavity et al. All of these
processes determine the shrinkage and stress and their development, which
are believed to be associated directly to a failure restoration.

[0017]This invention involves a chemical approach to limit polymerization
shrinkage and stress. More particularly it regards a new resin and its
composition development. In this invention, therefore, a general method
is presented to make a polymerizable single net, such as a polymerizable
macrocyclic oligomer, from which a 3D network would be developed via less
direct polymerization of (meth)acrylate. Now the whole picture is clear:
to pre-build a polymerizable macrocyclic as single net outside the tooth
cavity first, then assembly it into a network inside the filled cavity
with limited reaction. As a result for this new approach, the total
shrinkage would be reduced due to the limited reaction group. However,
the necessary mechanical property would not be significantly impaired
because the cyclic nature can make easy in cross-link density
development. In addition, a new mono(meth)acrylate with bulky side group
was combined with the macrocyclic resin to generate a resin system that
afford better balance regarding mechanical strength, polymerization
shrinkage ands contraction stress. Finally a proper glass filler
composition is also presented which determine the mechanical strength and
handling property as well.

[0018]Various macrocyclic oligomers are well investigated since the
researchers at GE developed a new approach to prepare cyclic carbonate
oligomers. For example, in U.S. Pat. No. 4,644,053, it was disclosed a
method to synthesize single macrocyclic compounds. Then various
macrocyclics oligomers, including carbonates, esters, amides, ethers,
imides, sulfides, et al, have been prepared. However, high temperature
ring-opening reaction has to be involved to convert these macrocyclics
into high molecular weight polymers. None of them could be further
polymerizable without ring-opening.

[0019]Many photopolymerizable resins have been developed from mono-, di-
or multiple functional resins to dendrimer, but no macrocyclic oligomer
with multipolymerizable groups has been reported: U.S. Pat. No.
5,047,261, disclosed a composition containing a five-member carbonate
cyclic group for fast copolymerization with mathacrylate.

[0020]U.S. Pat. No. 5,962,703, disclosed functionalized bicyclic
methacrylate with norboneyl or norbonadienl group. U.S. Pat. No.
5,792,821, disclosed polymerizable cyclidextrin (CD) derivatives, in
which various methacrylate was attached on CD. More recently, U.S. Pat.
No. 6,043,361, disclosed polymerizable cyclic allylic sulfides is used
for low shrinkage materials. All of these cyclic-related new resins are
limited to small cyclic sizes that are exclude in the scope of this
invention.

[0021]The occurrence of cyclization reaction is favorite at high dilution
condition. However, its efficiency limits its possible application in
commercial development. Fortunately a pseudo-high-dilution technology was
developed to solve this problem. This technique was adopted here to
prepare a polymerizable macrocyclic oligomers. More specifically, a
free-radically polymerizable macrocyclic oligomers are prepared under
pseudo-high-dilution condition via a condensation reaction between a
reactive and free radical polymerizable precursor and various coupling
agents. With such a method, various macrocyclics could be formed via any
linkage to afford carbonate, ester, siloxane, phosphonate, and et al
derivatives. On the other hand, the condensation groups usually have to
be activated to assure a mild reaction for cyclization with the coupling
monomers in order to avoid any premature polymerization of the
pre-attached methacrylate groups. Typical reaction scheme is illustrated
as following:

##STR00001##

[0022]A: any aromatic or aliphatic or the combination moiety; [0023]B: any
linkage such as ether, thioether, ester, amide, carbonate, urethane, and
urane, et al; [0024]X: any reactive group such as hydroxyl, carboxyl, et
al [0025]Z: polymerizable groups like (meth)acrylate, vinyl, vinyl ether,
and epoxy, et al [0026]R: any aromatic or aliphatic or the combination;
[0027]Y: any activated groups such as acylidied, acylamide, formated,
carbonamade; [0028]D: any of aromatic or aliphatic or their combination
moiety;

[0029]The reactive monomer can be synthesized or commercially-available;
It may not contain the primary polymerizable groups but the coupling
agent must have at least one such a polymerizable group to ensure the
formation of resulting, macrocyclic oligomer to be further free-radical
polymerizable.

##STR00002##

[0030]A: Ar, cyclohexyl, [0031]B: O, COO,

##STR00003##

[0032]BisGMA is one of widely used dental resin and it contains two free
radical polymerizable group, methacrylate and two hydroxyl groups. This
turns BisGMA an ideal candidate for polymerizable macrocyclic oligomer,
although the presence of BisGMA isomer would make more complicated to
this approach. As shown in Scheme II, carbonyldiimidazol (CDI, 1), was
used to selectively reacted with the secondary alcohol in BisGMA (2) to
give an activated BisGMA, DIZ-BisGMA (3). It was isolated and the
chemical structure of DIZ-BisGMA was fully characterized with FITR and
NMR. According to the recent report by Davis et al, CDI and its
intermediates could exhibit surprisingly specificity towards primary,
secondary, tertiary functional groups, of the same type, during the
controlled formation of various well-defined molecular
sequences.sup.[1-5]. In this invention, our idea is to adopt same
chemistry of CDI and to selectively activate the two secondary hydroxyl
groups in a free-radically polymerizable diol, BisGMA. Furthermore, the
resulting precursor, DIZ-BisGMA, was made to react with various primary
diols under a pseudo high-dilution condition, as shown in Scheme III, to
generate macrocyclic carbonate oligomer bearing multiple polymerizable
methacrylate groups. The two reactants were charged into the system in a
high-dilution condition via two liquid pumps with slowly, precisely
controlled addition in order to ensure a favorable formation of cyclic
product. Actually cyclic product is accumulated within the reaction
system and the final concentration can reach 0.02M, which is much higher
than the classical high dilution condition (0.001M). However, the key to
this procedure is to maintain a low initial concentration of reactants by
controlled feeding. Therefore, it is referred as pseudo-high-dilution
(PHD) method. The following examples will present the detailed procedure
of the preparation of various precursors, macrocyclic oligomers, new
cyclic diluent and composites thereafter.

EXAMPLE 1

[0033]34.4 g CDI was charged into a 1 liter, 3-neck round flask, which is
equipped with a mechanic stirrer, condenser and nitrogen inlet. Then 200
ml of methylene chloride were added and slurry was formed. Once 140 ml
solution of BisGMA in methylene chloride was introduced to the flask, the
reaction system turned clear immediately. Allow the reaction run at room
temperature for additional 4 hours before it was transfer to a volumetric
flask. Be aware to add more solvent to bring up final volume of 500 ml,
which is the necessary amount for next step macrocyclic reaction. It is
not necessary to isolate the by-product from the precursor at this point
because same compound will be generated during next cyclization process
and it is not harmful to the cyclization as well. Sample can be taken
from the final solution for FTIR analysis. Typical OH band should be
totally disappeared and new carbonyl peak shifted to 1765 cm-1 from
1718-1720 cm-1 in BisGMA. If the precursor is isolated and purified,
quantitative yield will be got.

EXAMPLE 2

[0034]Set up a 4 liter, 3-neck round flask, which is equipped with a
mechanic stirrer, condenser and a two-arm liquid inlet. Connect the two
liquid inlet arms to two separate liquid pumps, which will pump the two
reactants, 500 ml each, into the reaction vessel at a controlled rate.
The 500 ml of precursor prepared as above as one reactant, and another
500 ml solution of TetraEG (19.5 g) in methylene chloride as second
reactant. Then add 40.0 g of potassium carbonate, 4.0 g of tetrabutyl
ammonium bromide, 0.05 g of BHT, and 2000 ml of methylene chloride into
the reaction vessel at room temperature. Then start to pump the two
solutions into the reaction system at a rate of 80 ml per hour. All of
the solution would be charged into the system in about 6-6.5 hrs. Then
allow the reaction continue for additional 10-12 hrs before it was
filtered to remove any solid. Part of the solvent can be stripped off and
extracted the resulting solution with dilute acid, base and neutral water
for several time to purify the product. Then the extracted solution was
dried in magnium sulfate before removing all of the solvent. Clear,
pale-yellow viscose resin is obtained. FTIR analysis confirmed the
formation of cyclic carbonate by the carbonyl peak shifted back to 1740
cm-1 and less OH absorption at 3500-3800 cm-1, which suggest no or at
least much less of the existence of hydroxyl end group. NMR and GPC
analysis also support the formation of cyclic structure. It is mixture of
macrocyclics with different size, and small amount of linear derivative
is also evident. The overall yield of macrocyclic carbonate oligomer can
be more than 95%.

EXAMPLE 3-15

[0035]Followed this general synthesis process as present in Example 2,
instead of TetraEG, various diols were explored to prepare different
macrocyclic carbonate oligomers.

EXAMPLE 16

[0036]As illustrated in example 1, new reactive dimethacylate, IPADMA was
used instead of BisGMA to form different activated precursor; and
accordingly, new macrocyclic carbonate was prepared.

EXAMPLE 17

[0037]As illustrated in Example 1, trichloride phosphonate was used in
reaction with BisGMA to developing an activated phosphate, which then was
used to form a macrocyclic phonate bearing polymerizable groups.

EXAMPLE 18

[0038]Dissolve 3.0 g DMAP and 98.2 g TCDCOH in 250 ml of THF and 250 ml of
methylene chloride. Then add 90 ml TEA into this solution before it was
transferred to a 1 liter, 3-neck round flask setting in an ice bath of
0-5° C., which is equipped with a mechanic stirrer, condenser and
a 200 ml addition funnel. Then 93.2 g of MAA in 100 ml of methylene
chloride were added the addition funnel. Start to add the MAA solution
dropwisely into the reaction system in a period of 2-3 hrs. Keep the
reaction temperature around at 0-5° C. Allow the reaction to
continue for additional 3-4 hrs after all of MAA solution was charged
into the system. Extracted the resulting reaction solution with dilute
acid, base and neutral solution, it was dried and further stripped to
result a clear, colorless liquid. This is a mixture of dimethacrylate and
monomethacrylate. The radio for TCDCDMA and TCDCMA is 1:5 to 1:2, more
preferably is 1:3. FTIR analysis can verify the actual ratio. New
carbonyl peak shifted to 1765 cm-1 from 1778-1810 cm-1 in MAA.
Quantitative yield is for this TCDCMA/TCDCDMA mixture.

EXAMPLE 19

[0039]As illustrated in Example 2, an improved process was developed by
add TCDCMA/TCDCDMA mixture into the resulting macrocyclic oligomer
solution prior to final strip mixture. The weight ratio for this cyclic
resin and the diluent resin should keep in about 2:1. This would make
easy for the solvent removal and increase resin stability. The viscosity
for this resin mixture can be 150-200 Pas at 25° C.

EXAMPLE 20

[0040]As illustrated in Example 19, the resulting resin mixture will
formulate with additional 10-15% (wt/wt) of TCDCA (Aldrich) to result in
proper resin mixture for low shrink composite. Its viscosity range from
50-75 Pss at 25° C.

EXAMPLE 21

[0041]CQ, EDAB, BHT and other necessary additives were admixed with the
above resin mixture accordingly.

EXAMPLE 22

[0042]Glass filler mixtures with three different size distribution were
premixed in as ration 60/20/20 or more preferably 55/30/15
(medium/coarse/fine particle).

EXAMPLE 23

[0043]Composite paste was made from 18-20% of the above-mentioned resin
mixture and 80-82% BAFG filler mix. Its polymerization shrinkage ranged
from 1.10-30% by dilatometer to 0.80-1.20% by gas pycnometer. This paste
is condensable and demonstrated excellent packability with packability
index of 1000 g/mm2. It can be easily extruded from a 2.1 mm compule with
a typical extrusion force of 10 kgf. It has moderate overall mechanical
strength such as compressive strength of 300 Mpa, compressive modulus of
7400 Mpa, flexural strength of 110-120 Mpa and flexural modulus is
9900-10000 Mpa. The 400K cycle local wear index is 0.05. The most
important feature id its low curing strain of 750-850 ue, which is about
1/2 of TPH (1647) or SureFil (1865) composite.

COMPARISON EXAMPLE 1

[0044]Similar composite paste made from 18-20% of the conventional NCO
monomers and 80-81% BAFG filler mix as presented by SureFil. It has
polymerization shrinkage 2.30-2.20% by dilatometer or 2.50% by gas
pycnometer, which are more 100% higher than the current experimental
composite. SureFil possesses a packability index of 800 g/mm2. It also
has superior mechanical property such as compressive strength of 340 Mpa,
flexural strength of 140 Mpa and flexural modulus of 1200 Mpa. The 400K
cycle local wear index is as low as 0.02. However, its curing strain
reached 1865 ue, which is 130% higher than the experimental composite.
This means the polymerization stress would be doubled in SureFil.

COMPARISON EXAMPLE 2

[0045]Another composite paste made from 22-23% of the conventional NCO
monomers and 77-78% BABG filler mix as presented by TPH Spectrum. It has
polymerization shrinkage 2.60-2.80% by dilatometer or 2.90% by gas
pycnometer, which are more 100% higher than the current experimental
composite. TPH Spectrum is not a packable materials, even it has
excellent mechanical strength such as compressive strength of 380 Mpa,
flexural strength of 130 Mpa and flexural modulus of 1100 Mpa. The 400K
cycle local wear index is 0.06. Curing strain is 1650 ue, which is 110%
higher than the experimental composite.

COMPARISON EXAMPLE 3

[0046]Another composite paste based on 21-22% of the different
conventional resin mixture and more than 78% of BABG filler mix
containing small amount nano-filler as presented by Experimental
composite II. It has polymerization shrinkage 1.60% by dilatometer or
2.10% by gas pycnometer, which at least is 50% higher than the current
experimental composite. This is a less packable materials, its
packability index is only 650. But it does demonstrated good overall
mechanical strength such as compressive strength of 320 Mpa, flexural
strength of 110 Mpa and flexural modulus of 9000 Mpa. However, its curing
strain is 1120 ue, which is 40% higher than the current experimental
composite.